Monensin, a polyether antibiotic, acts as a sodium-selective ionophore, and when given in large doses it produces toxicosis with myocardial and skeletal muscle necrosis. The monensin model of necrosis presents certain unique features, related to the fact that the primary effect of this agent is to increase sodium entry into cells. This study provides a detailed characterization of the clinical and pathologic features of the cardiac necrosis induced by monensin.